CaP-Coated Cyclosporine A Liposomes Formulated as an Inhalable Dry Powder for Lung Inflammatory Diseases

Abstract Background: Cyclosporine is widely used to prevent transplant rejection; however, its systemic administration is associated with low bioavailability and a risk of severe adverse side effects. In the context of lung transplantation, local pulmonary delivery represents a promising strategy to reduce the required dose while enhancing local anti-inflammatory efficacy and limiting systemic toxicity. Methods: In this study, cyclosporine was encapsulated in liposomes coated with calcium phosphate to improve cellular uptake. The liposomal formulation was subsequently converted into a dry powder for inhalation to enable pulmonary administration, combining cyclosporine-loaded liposomes with a calcium phosphate coating, extending prior work on inhaled liposomal cyclosporine and mineral-coated liposomes into a single platform. The cyclosporine loading was optimised to achieve an efficient drug content in the final formulation. Results: The presence of the calcium phosphate coating on the liposomal surface was confirmed by the shift in zeta potential and by cryo-transmission electron microscopy. The resulting dry powder exhibited suitable aerodynamic properties for pulmonary delivery with a fine particle fraction of 33.6 ± 1.6%. In vitro biocompatibility studies performed on A549 epithelial cells and THP-1 monocytic cells demonstrated that the formulation did not affect cell viability. Furthermore, the formulation containing calcium phosphate-coated liposomes showed a stronger anti-inflammatory effect compared with both uncoated liposomal formulations and the corresponding raw material, consisting of a physical mixture of phospholipids and cyclosporine. Conclusions: Overall, despite limitations on respirability and efficacy that will require further in vivo studies, this calcium phosphate-coated liposomal dry powder could represent a promising strategy for targeted pulmonary delivery of cyclosporine, with potential to improve the prevention of lung transplant rejection while minimising systemic side effects.